The cell adhesion is generally classified according to two categories, i.e. a first category relative to the adhesion between a cell and a substrate and a second category relative to the adhesion between two cells. The present invention relates to the first category of cell adhesion cellular between the cell and the substrate.
Most cells are adherent to a substrate, except for a few exceptions like hematopoietic cells for example. Adhesion of a cell to a substrate is a complex process involving diverse proteins. In addition to diverse other functions such as metastasis, healing of wounds, differentiation of tissues, the adhesion of a cell to a substrate forms a communication means between the cell and its environment. This communication is required for migration and proliferation of the cells. Incapability of the cells of adhering to the substrate may lead to their death.
Studying the adhesion of the cell to the substrate is therefore important for analyzing the fundamental processes associated with the cell. Such a study may provide an answer to questions concerning the relationships between the structure and function of cell adherence molecules and their respective ligands. Such a study is moreover able to provide information on the connection between the individual adhesive properties of cells and their capability of acting in a multi-cell environment, upon examining processes such as growth, angiogenesis, invasion, extravasation, metastasis, synthesis of proteins of the matrix or further secretion of degradation enzymes. Studying the adhesion of the cell to the substrate is finally a useful tool in the screening of reagents which interfere with cell adhesion to substrates, or further promotes it, as this was described in the article “Enzymatic quantification of cell-matrix and cell-cell adhesion”, of Löster et al., published in the journal Micron, Volume 31, Number 1, pages 41 to 53, in January 2000.
Different techniques for studying the adhesion of the cell to the substrate have been described in the aforementioned article, in the article “Cell adhesion assays” of M. J. Humphries, published in the journal Methods in molecular biology, Volume 522, pages 203 to 210, in January 2009, as well as in the article “Heterotypic Cell Adhesion Assay for the Study of Cell Adhesion Inhibition” of Satyanarayanajois et al., published in the journal Drug Design and Discovery.
These techniques involve different handling operations, typically additions of reagents in the liquid, followed by multiple washes and multiple optical acquisitions (microscopy, cytometry, optical density). In fact, they are costly in reagents and in manpower time and remain difficult to apply. In particular, they strongly depend on the efficiency of the reagent. More importantly, they do not allow or only with difficulty the carrying out of measurements continuously over time. Further, they do not give the possibility of following individually thousands of cells which reduces the statistical quality of the measurement, beyond the use of a marker and/or of a reagent which may interfere with the life of the cell which biases the measurement. In the worst case, the method is destructive of the sample: the fluorescent marking associated with a cytometry measurement is destructive for the sample.